Comparison of cerebrovascular effects of intravenous cocaine injection in fetal, newborn, and adult sheep

2000 ◽  
Vol 279 (1) ◽  
pp. H1-H6 ◽  
Author(s):  
Roderick Robinson ◽  
Hiroki Iida ◽  
Thomas P. O'Brien ◽  
Maria A. Pane ◽  
Richard J. Traystman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Species Differences ◽  
Developmental Differences ◽  
Metabolic Responses ◽  
Cerebral Vasoconstriction ◽  
Arterial Blood ◽  
Cerebral Vasodilation ◽  
Cerebral Vascular Resistance ◽  
Intravenous Cocaine

Cocaine may cause stroke, intracranial hemorrhage, seizures, and neurobehavioral abnormalities in fetuses, newborns, and adults, and there could be developmental and/or species differences in mechanisms for these cocaine-induced cerebrovascular effects. To evaluate developmental differences in responses to cocaine, we compared the cerebrovascular and metabolic responses to a 2 mg/kg iv cocaine dose in unanesthetized fetal ( n = 8, previously reported, direct fetal injection), newborn ( n = 6), and adult ( n = 12) sheep. We measured cerebral blood flow, mean arterial blood pressure, and arterial and venous O2content, and we calculated cerebral O2consumption and cerebral vascular resistance at baseline and at 30 s and at 5, 15, and 60 min after cocaine injection. Cerebral blood flow increased 5 min after injection in the fetus and newborn, but not until 15 min in the adult. In the fetus, cocaine caused a transient cerebral vasoconstriction at 30 s; in all three groups, cocaine caused cerebral vasodilation, which was delayed in the adult. Cerebral metabolic O2consumption increased 5 min after injection in the fetus and newborn, but not until 15 min after injection in the adult. Arterial O2content decreased 5 min after injection in the fetus and 15 min after injection in the adult. We speculate that clinical differences in response to cocaine injection may be explained, in part, by these developmental differences in the cerebrovascular and metabolic responses to cocaine.

Vasopressin and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs

1990 ◽  
Vol 258 (2) ◽  
pp. H408-H413 ◽  
Author(s):  
W. M. Armstead ◽  
C. W. Leffler ◽  
D. W. Busija ◽  
R. Mirro
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Vascular Resistance ◽  
Brain Regions ◽  
Cerebral Metabolic Rate ◽  
Cerebral Vasoconstriction ◽  
Newborn Pigs ◽  
Cerebral Vascular Resistance ◽  
Cerebral Vascular

The interaction between vasopressinergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious hypotensive newborn pig was investigated. Indomethacin treatment (5 mg/kg) of hypotensive piglets caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 52 and 198% 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.58 +/- 0.32 ml.100 g-1.min-1 to 1.01 +/- 0.12 and 0.29 +/- 0.08 ml.100 g-1.min-1 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Treatment with the putative vascular (V1) receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine]arginine vasopressin (MEAVP) had no effect on regional cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or during hemorrhagic hypotension. However, decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were blunted markedly in animals treated with MEAVP. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn pig, as reported previously, and implicate removal of vasopressinergic modulation by prostanoids as a potential mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets.

scholarly journals Differential contribution of cyclooxygenase to basal cerebral blood flow and hypoxic cerebral vasodilation

2020 ◽  
Vol 318 (2) ◽  
pp. R468-R479 ◽  
Author(s):  
J. Mikhail Kellawan ◽  
Garrett L. Peltonen ◽  
John W. Harrell ◽  
Alejandro Roldan-Alzate ◽  
Oliver Wieben ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Arteries ◽  
Relative Increase ◽  
Cross Sectional ◽  
Arterial Blood ◽  
Intracranial Arteries ◽  
Fraction Of Inspired Oxygen ◽  
Cerebral Vasodilation ◽  
Relative Change

Cyclooxygenase (COX) is proposed to regulate cerebral blood flow (CBF); however, accurate regional contributions of COX are relatively unknown at baseline and particularly during hypoxia. We hypothesized that COX contributes to both basal and hypoxic cerebral vasodilation, but COX-mediated vasodilation is greater in the posterior versus anterior cerebral circulation. CBF was measured in 9 healthy adults (28 ± 4 yr) during normoxia and isocapnic hypoxia (fraction of inspired oxygen = 0.11), with COX inhibition (oral indomethacin, 100mg) or placebo. Four-dimensional flow magnetic resonance imaging measured cross-sectional area (CSA) and blood velocity to quantify CBF in 11 cerebral arteries. Cerebrovascular conductance (CVC) was calculated (CVC = CBF × 100/mean arterial blood pressure) and hypoxic reactivity was expressed as absolute and relative change in CVC [ΔCVC/Δ pulse oximetry oxygen saturation ([Formula: see text])]. At normoxic baseline, indomethacin reduced CVC by 44 ± 5% ( P < 0.001) and artery CSA ( P < 0.001), which was similar across arteries. Hypoxia ([Formula: see text] 80%–83%) increased CVC ( P < 0.01), reflected as a similar relative increase in reactivity (% ΔCVC/−Δ[Formula: see text]) across arteries ( P < 0.05), in part because of increases in CSA ( P < 0.05). Indomethacin did not alter ΔCVC or ΔCVC/Δ[Formula: see text] to hypoxia. These findings indicate that 1) COX contributes, in a largely uniform fashion, to cerebrovascular tone during normoxia and 2) COX is not obligatory for hypoxic vasodilation in any regions supplied by large extracranial or intracranial arteries.

Ventilatory, cerebrovascular, and cardiovascular interactions in acute hypoxia: regulation by carbon dioxide

2004 ◽  
Vol 97 (1) ◽  
pp. 149-159 ◽  
Author(s):  
Philip N. Ainslie ◽  
Marc J. Poulin
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Blood Flow Velocity ◽  
Acute Hypoxia ◽  
Random Order ◽  
Transcranial Doppler Ultrasound ◽  
Individual Variability ◽  
Cerebral Vasoconstriction ◽  
Arterial Blood ◽  
End Tidal

This study examined the effect of high, normal, and uncontrolled end-tidal Pco2 (PetCO2) on the ventilatory, peak cerebral blood flow velocity ( V̄p), and mean arterial blood pressure (MAP) responses to acute hypoxia. Nine healthy subjects undertook, in random order, three hypoxic protocols (end-tidal Po2 was held at eight steps between 300 and 45 Torr) in conditions of hypercapnia, isocapnia, or poikilocapnia (PetCO2 +7.5 Torr, +1.0 Torr, or uncontrolled, respectively). Transcranial Doppler ultrasound was used to measure V̄p in the middle cerebral artery. The slopes of the linear regressions of ventilation, V̄p, and MAP with arterial O2 saturation were significantly greater in hypercapnia than in both isocapnia and poikilocapnia ( P < 0.05). Strong, significant correlations were observed between ventilation, V̄p, and MAP with each PetCO2 condition. These data suggest that 1) a high acute hypoxic ventilatory response (AHVR) decreases the acute hypoxic cerebral blood flow responses during poikilocapnia hypoxia, due to hypocapnic-induced cerebral vasoconstriction; and 2) in hypercapnic hypoxia, a high AHVR is associated with a high acute hypoxic cerebral blood flow response, demonstrating a linkage of individual sensitivities of ventilation and cerebral blood flow to the interaction of PetCO2 and hypoxia. In summary, the between-individual variability in AHVR is shown to be firmly linked to the variability in V̄p and MAP responses to hypoxia. Individuals with a high AHVR are found also to have high V̄p and MAP responses to hypoxia.

Regional distribution of cerebral blood flow during exercise in dogs

1980 ◽  
Vol 48 (2) ◽  
pp. 213-217 ◽  
Author(s):  
P. M. Gross ◽  
M. L. Marcus ◽  
D. D. Heistad
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Distribution ◽  
Moderate Intensity ◽  
Regional Cerebral Blood ◽  
Arterial Pco2 ◽  
Regional Flow ◽  
Arterial Blood ◽  
The Brain ◽  
Cerebral Vascular Resistance

This study was performed to determine whether exercise produces vasodilatation in regions of the brain that are associated with motor functions despite the associated vasoconstrictor effect of hypocapnia. Total and regional cerebral blood flow (CBF) were measured with microspheres in dogs during treadmill exercise of moderate intensity. Flow was also measured at rest after stimulation of ventilation with doxapram. During moderate exercise, total CBF was not changed significantly, but regional flow was increased in structures associated with motor-sensory control; blood flow to motor-sensory cortex, neocerebellar and paleocerebellar cortex, and spinal cord increased 30 +/- 7%, 39 +/- 8%, and 29 +/- 4%, respectively (P less than 0.05). After doxapram, which increased arterial blood pressure and decreased arterial PCO2 to levels similar to those during exercise, total CBF decreased and there was no redistribution of CBF. These results indicate that exercise in conscious dogs increases blood flow in regions of the brain associated with movement despite the associated vasoconstrictor stimulus of arterial hypocapnia. Thus, during exercise, local dilator influences that presumably result from increases in metabolism predominate over a potent constrictor stimulus in regulation of cerebral vascular resistance.

Chemical regulation of cerebral blood flow in turtles

1991 ◽  
Vol 260 (2) ◽  
pp. R382-R384 ◽  
Author(s):  
D. G. Davies
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Anaerobic Metabolism ◽  
Extracellular Fluid ◽  
Freshwater Turtles ◽  
Arterial Pco2 ◽  
Arterial Blood ◽  
Radioactive Microsphere ◽  
Radioactive Microsphere Technique ◽  
Cerebral Vascular Resistance

This study was performed to test the effect of the chemical composition of the blood on cerebral blood flow (CBF) regulation in turtles. The CBF response to increases in arterial PCO2 (PaCO2) (hypercapnia) was measured during normoxia and anoxia in anesthetized freshwater turtles Pseudemys scripta. The radioactive-microsphere technique was used to measure CBF. CBF increased with increases in PaCO2. The sensitivity of the CBF response to hypercapnia (delta CBF/delta PaCO2) was 0.68 ml.min-1.100 g-1. Torr-1 during normoxia. delta CBF/delta PaCO2 increased to 3.44 ml.min-1.100 g-1. Torr-1 during anoxia. The increases in CBF occurred at constant mean arterial blood pressure, which indicates that cerebral vascular resistance decreased. The increased CBF response during asphyxia (hypercapnia-anoxia) could be beneficial for survival during prolonged dives by increasing glucose delivery for brain anaerobic metabolism. In addition, increased CBF could aid in regulating brain acid-base composition by controlling extracellular fluid PCO2.

Adrenergic and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs

1988 ◽  
Vol 254 (4) ◽  
pp. H671-H677
Author(s):  
W. M. Armstead ◽  
C. W. Leffler ◽  
D. W. Busija ◽  
D. G. Beasley ◽  
R. Mirro
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Vascular Resistance ◽  
Brain Regions ◽  
Cerebral Metabolic Rate ◽  
Cerebral Vasoconstriction ◽  
Sympathetic Modulation ◽  
Cerebral Vascular Resistance ◽  
Cerebral Vascular

The interaction between adrenergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious, hypotensive newborn pig was investigated. Pretreatment with the selective alpha 1- and alpha 2-adrenoceptor antagonists prazosin and yohimbine, respectively, had no effect on cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or after hemorrhagic hypotension. Indomethacin treatment (5 mg/kg ia) of piglets following hemorrhage caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 54 and 177%, 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.42 +/- 0.28 to 1.45 +/- 0.28 ml.100 g-1.min-1 and to 1.0 +/- 0.28 ml.100 g-1.min-1 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were the same as in animals pretreated with vehicle, prazosin, or yohimbine. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn, as reported previously. These data do not implicate removal of sympathetic modulation by prostanoids as a mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets.

scholarly journals Examination of Potential Mechanisms in the Enhancement of Cerebral Blood Flow by Hypoglycemia and Pharmacological Doses of Deoxyglucose

1997 ◽  
Vol 17 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Naoaki Horinaka ◽  
Nicole Artz ◽  
Jane Jehle ◽  
Shinichi Takahashi ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
Insulin Hypoglycemia ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Arterial Plasma

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 m M, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3– concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 m M) or pharmacological doses of deoxyglucose.

scholarly journals Cerebral blood flow autoregulation in ischemic heart failure

2017 ◽  
Vol 312 (1) ◽  
pp. R108-R113 ◽  
Author(s):  
J. R. Caldas ◽  
R. B. Panerai ◽  
V. J. Haunton ◽  
J. P. Almeida ◽  
G. S. R. Ferreira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Healthy Volunteers ◽  
Neurological Complications ◽  
Ischemic Heart ◽  
Step Response ◽  
Ischemic Heart Failure ◽  
Arterial Blood ◽  
End Tidal

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20–45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.

Diurnal variation in time to presyncope and associated circulatory changes during a controlled orthostatic challenge

2010 ◽  
Vol 299 (1) ◽  
pp. R55-R61 ◽  
Author(s):  
N. C. S. Lewis ◽  
G. Atkinson ◽  
S. J. E. Lucas ◽  
E. J. M. Grant ◽  
H. Jones ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Diurnal Variation ◽  
Flow Velocity ◽  
Blood Flow Velocity ◽  
Cerebral Blood Flow Velocity ◽  
Orthostatic Challenge ◽  
Arterial Blood ◽  
Neurally Mediated Syncope

Epidemiological data indicate that the risk of neurally mediated syncope is substantially higher in the morning. Syncope is precipitated by cerebral hypoperfusion, yet no chronobiological experiment has been undertaken to examine whether the major circulatory factors, which influence perfusion, show diurnal variation during a controlled orthostatic challenge. Therefore, we examined the diurnal variation in orthostatic tolerance and circulatory function measured at baseline and at presyncope. In a repeated-measures experiment, conducted at 0600 and 1600, 17 normotensive volunteers, aged 26 ± 4 yr (mean ± SD), rested supine at baseline and then underwent a 60° head-up tilt with 5-min incremental stages of lower body negative pressure until standardized symptoms of presyncope were apparent. Pretest hydration status was similar at both times of day. Continuous beat-to-beat measurements of cerebral blood flow velocity, blood pressure, heart rate, stroke volume, cardiac output, and end-tidal Pco2 were obtained. At baseline, mean cerebral blood flow velocity was 9 ± 2 cm/s (15%) lower in the morning than the afternoon ( P < 0.0001). The mean time to presyncope was shorter in the morning than in the afternoon (27.2 ± 10.5 min vs. 33.1 ± 7.9 min; 95% CI: 0.4 to 11.4 min, P = 0.01). All measurements made at presyncope did not show diurnal variation ( P > 0.05), but the changes over time (from baseline to presyncope time) in arterial blood pressure, estimated peripheral vascular resistance, and α-index baroreflex sensitivity were greater during the morning tests ( P < 0.05). These data indicate that tolerance to an incremental orthostatic challenge is markedly reduced in the morning due to diurnal variations in the time-based decline in blood pressure and the initial cerebral blood flow velocity “reserve” rather than the circulatory status at eventual presyncope. Such information may be used to help identify individuals who are particularly prone to orthostatic intolerance in the morning.

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